Virtual Library

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    OA11 - Thymic and Other Thoracic Tumours: Targeted Therapies, Biomarkers and Neo/Adjuvant Radiotherapy (ID 919)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 7
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 205 BD
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      OA11.01 - Role of Post-Operative Radiation in Different Histologic Subgroups of Thymoma: Result Based on National Cancer Data Base (NCDB) (ID 14353)

      13:30 - 13:40  |  Presenting Author(s): Tithi Biswas  |  Author(s): Asoke Dey, Tarun Podder

      • Abstract
      • Presentation
      • Slides

      Background

      Thymoma and thymic carcinoma are rare neoplasms that occur in the anterior mediastinum. According to WHO classification, thymomas are classified into 5 different subgroups based on their clinical behavior. The role of post-operative radiation (PORT) has been studied well based on the stage grouping. However, the benefit of PORT on different histologic subtypes is not well defined. We analyzed role of PORT in 5 different subgroups of thymomas using NCDB data base.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From 2004-2014, using C37.9 topographic code, 6532 patients were identified with a diagnosis of thymoma or thymic carcinoma. The median age was 60 years. 48.6% were male. 78.5% (n=5127) patients underwent surgery and 52.4% (n=3425) did not receive any radiation. Patients with no surgery and with thymic carcinoma histology were excluded. Patients with thymoma who had radiation dose between 40-60 Gy were included for the final survival analysis. Overall survival (OS) was calculated using Kaplan Meier method with log rank test for comparison analysis. IBM SPSS (v24) was used for statistical analysis; p-value of <0.05 was considered statistically significant.

      4c3880bb027f159e801041b1021e88e8 Result

      Thymic carcinoma was the most frequent subtype (20.6%) followed by AB subtype (14.4%). Type A was least frequent subtype (7.7%) while 22.3% did not have any subclassification. 48.1% (n=3139) had no residual cancer, 12% had microscopic involvement and 2.6% had macroscopic residual cancer. Macroscopic tumors were more frequently seen with thymic carcinoma (3.43%) and B1 (1.23%), B3 (1.43%) subtypes. Median overall survival with surgery was 8 years compared to approximately 10 years with PORT (p<0.0001) for the entire group. Among 5 subcategories, PORT was associated with improved OS for type A (p<0.007), AB (p=0.008) and B3 (p=0.003). For B1, PORT was associated with inferior OS and for B2, PORT was not significant for OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this analysis PORT was associated with statistically significant improved OS in A, AB and B3 subgroups but not for B2 and B3. Further work is underway to perform multivariable analysis.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA11.02 - A Population-Based Study of Incidence and Survival Trends of 1,588 Thymic Malignancies: Results from the California Cancer Registry (ID 12459)

      13:40 - 13:50  |  Presenting Author(s): David Joseph Benjamin  |  Author(s): Amy Klapheke, Primo Lara, Rosemary Cress, Jonathan W Riess

      • Abstract
      • Presentation
      • Slides

      Background

      Thymic malignancies (TM) are rare with sparse population-based epidemiologic literature. According to data collected by the National Cancer Institute from 1973 to 2006, the incidence of thymomas is 0.13 per 100,000 person-years in the United States.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We used data from the California Cancer Registry (CCR), a comprehensive population-based state registry to examine TM incidence and survival trends in California from 1988 to 2015. Cases were specified by site (thymus), histology (thymic carcinoma and thymoma), and behavior (malignant). Primary endpoints were cause-specific survival (CSS) and overall survival (OS). Age-adjusted incidence rates were calculated in SEER*Stat, and Joinpoint regression was used to analyze incidence trends. Hazard ratios (HR) for CSS and OS were calculated using a Cox proportional hazards regression model controlling for relevant baseline variables including age, gender, stage, and year of diagnosis, among others.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified 1,588 TM cases in California from 1988 to 2015 with an annual percent increase of 2.08% (95% CI: 1.3%, 2.9%; p < 0.0001). The incidence of TM in 2015 was 0.277 per 100,000. Thymic carcinoma histology was associated with worse CSS across all stages, including localized (HR 7.56, 95% CI 1.44, 39.78), regional (HR 4.23, 95% CI 2.55, 7.01), and remote (HR 2.09, 95% CI 1.37, 3.19) disease. Compared to no treatment, surgery with or without radiation was associated with improved CSS in localized (surgery: HR 0.05 (95% CI 0.01 to 0.35), surgery + radiation: HR 0.12 (95% CI 0.02 to 0.84)) and regional disease (surgery: HR 0.11 (95% CI 0.04 to 0.29), surgery + radiation: HR 0.15 (95% CI 0.06 to 0.36)). Chemotherapy and radiation was also associated with improved CSS in regional disease (HR=0.22 (95% CI 0.07 to 0.63) and remote disease (5.16 (0.37, 71.94)), though the latter was not statistically significant.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is a population-based study of TMs from the CCR that identifies baseline variables significantly associated with CSS. TM incidence appears to be increasing over time. Advanced stage and thymic carcinoma were found to be associated with worsened CSS, which is consistent with previous studies. Treatment incorporating surgery was associated with improved CSS in local and regional disease, as was chemoradiation in regional disease. Improvement in CSS trended towards significance in patients with remote thymic neoplasms treated with chemoradiation. These findings provide a more contemporary database for future TM outcomes research.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA11.03 - Discussant - OA 11.01, OA 11.02 (ID 14566)

      13:50 - 14:05  |  Presenting Author(s): Andrew Hope

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      OA11.04 - A Comparative Study of PD-L1 Immunohistochemical Assays with Four Reliable Antibodies in Thymic Carcinoma (ID 12114)

      14:05 - 14:15  |  Presenting Author(s): Tadashi Sakane  |  Author(s): Hiroshi Haneda, Katsuhiro Okuda, Keisuke Yokota, Tsutomu Tatematsu, Risa Oda, Takuya Watanabe, Yushi Saito, Takeshi Yamada, Ryoichi Nakanishi

      • Abstract
      • Presentation
      • Slides

      Background

      Currently, programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) targeted therapy has not been established for thymic carcinoma (TC) yet, and limited information is available regarding the expression pattern of PD-L1 in TC. Four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The clinicopathological data of 53 TC patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (22C3, 28-8, SP142, and SP263). We examined tumor proportion scores (TPS) in each case and the cutoff values were settled at 1% for 22C3, 1% for 28-8, 1% for SP142, and 25% for SP263. Date were correlated to clinicopathologic parameters and outcomes.

      4c3880bb027f159e801041b1021e88e8 Result

      The study population included 32 male patients and 21 female patients (median age, 61 years). In the TPS, the four assays showed similar scores in each case. Pairwise analyses of the TPS for the four assays showed high concordance among the four assays (the Spearman’s rank correlation coefficients were all >0.9). Histopathologically, high TPS was observed in squamous cell carcinomas (SqCCs). Using cutoffs, 34 cases (64.2%) with 22C3, 41 cases (77.4%) with 28-8, 43 cases (81.1%) with SP142, and 26 cases (49.1%) with SP263 were detected as PD-L1 positive. In SqCCs, the high expression of PD-L1 (TPS ≥50%) were associated with early stage cancer when evaluated with 22C3 (p=0.0205), 28-8 (p=0.0448), and SP263 (p=0.0486), respectively. However the high expression of PD-L1 were not associated with sex, age, tumor size, and curability. The SqCC patients with high expression of PD-L1 tended to show longer overall survival; p=0.0250 in 22C3, p=0.0719 in 28-8, p=0.1064 in SP142, and p=0.0675 in SP263.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The present study revealed that the TC patients, especially SqCC patients, showed high PD-L1 positivity and that the staining pattern showed high concordance among the four assays. High expression of PD-L1 might be a prognostic predictor, though observed effect was independent on the assay. Our results suggest that the PD-1/PD-L1 pathway is a potential immunotherapeutic target in TC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA11.05 - Phase II Study of Sunitinib in Patients with Thymic Carcinoma Previously Treated with Platinum-Based Chemotherapy (KOSMIC Trial) (ID 13228)

      14:15 - 14:25  |  Presenting Author(s): Se Hyun Kim  |  Author(s): Yu Jung Kim, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Jong Seok Lee

      • Abstract
      • Presentation
      • Slides

      Background

      Only one prospective study in western population suggests sunitinib is an effective treatment for thymic carcinoma (TC). We evaluated the clinical efficacy and toxicity of sunitinib in Korean patients with metastatic TC after platinum-based chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between Sep 2015 and May 2017, we enrolled 25 patients with histologically confirmed platinum-refractory TC at three academic hospitals in Korea. Patients were eligible if they had progressive disease after one or more cytotoxic chemotherapy including platinum-based regimen, at least one measurable disease by RECIST (v1.1) and adequate organ function. Patients received 50mg of sunitinib on an alternative schedule (2weeks of treatment followed by 1 week without treatment) until objective progression of disease or unacceptable toxicity of treatment. The primary endpoint was objective response rate and tissue and blood specimen were collected for NGS panel analysis (170 genes, Hybrid capture based method). This trial was registered with Clinicaltrials.gov, number NCT 02623127.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 25 patients were enrolled in this trial. Median age was 62 (39-75) and 19 (76%) patients were male. Most patients (20 patients, 80%) received sunitinib as 2nd line treatment. Two patients discontinued treatment earlier than first tumor assessment due to toxicity and excluded from efficacy analysis. Among 23 evaluable patients, 5 (21.7%) patients had partial response and 16 (69.6%) patients achieved stable disease. Disease control rate (PR+SD>6m) was 56.5%. Median progression-free survival (PFS) was 15.2 months and 6 patients had ongoing responses at the time of analysis. Most common treatment-related adverse events were mucositis (12 patients, 48%), fatigue (9 patients, 36%), and hand-foot syndrome (9 patients, 36%). The most common grade 3/4 toxicity was thrombocytopenia (4 patients, 16%). Seventeen (68%) patients needed at least one dose reduction due to adverse events. Genomic profiling with NGS cancer panel revealed 2 patients with pathogenic KIT mutation (c.1879+1G>A and c.1671 G>C) who had PFS of 21.3m and 9.3m, respectively. In 15 patients with tumor tissue gene panel results, high tumor mutation burden (TMB) was significantly associated with longer PFS (median PFS not reached in TMB ≥30/MB vs. 3.45m in TMB <30/MB, P=0.03).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Sunitinib with 2/1 schedule is an active treatment for TC after platinum-based chemotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA11.06 - Two BRM Promoter Polymorphisms Do Not Predict Susceptibility or Prognosis of Thymoma (ID 12745)

      14:25 - 14:35  |  Presenting Author(s): Nathan Kuehne  |  Author(s): Min Joon Lee, Katrina Hueniken, Daniel Shepshelovich, Sara Victoria Soldera, Sharara Shakik, Devalben Patel, Dangxiao Cheng, Zhuo Chen, Lawson Eng, M Catherine Brown, Andrea Bezjak, Shaf Keshavjee, David Reisman, Wei Xu, Geoffrey Liu

      • Abstract
      • Presentation
      • Slides

      Background

      Brahma (BRM) is a critical protein subunit in chromatin remodeling, and insertions/deletions at its two polymorphic promotor sites (BRM-741 and BRM-1321) have been reported as susceptibility and/or prognostic markers in lung, head and neck, esophageal, pancreatic, and liver cancers. There is also early evidence of potential association with immune-related diseases such as ulcerative colitis and rheumatoid arthritis. As epigenetic silencing of BRM can be pharmacologically reversed, BRM polymorphisms in cancer might have therapeutic implications. Thymoma is a unique cancer in that it has immunological disease associations. We evaluated whether BRM-741 and BRM-1321 polymorphisms influence overall risk, survival, and time-to-progression of thymoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Thymoma cases and matched healthy controls were recruited in a comprehensive cancer centre. Study participants’ peripheral blood samples were collected and genotyped for BRM promoter polymorphisms. Multivariable logistic regression assessed risk of thymoma in case-control analyses. Association of BRM variants with overall survival (OS) and time-to-progression or recurrence (TTP) was assessed by multivariable Cox regression.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 237 cases of histologically diagnosed thymoma and 948 age- and gender-matched healthy controls, thymoma patients had median age of 53 (range: 17-84) years; 121 (51%) were male; 76 (32%) had a history of myasthenia gravis. Median follow-up time was 7 years. 79% of patients were recurrence- and progression-free at 10-year follow-up (95% CI: 74-86%), and 81% of patients were alive at 10 years post-diagnosis (95% CI: 75-87%). Frequency of homozygous variants for either gene was not significantly different between thymoma cases and controls: homozygous BRM-741genotype (OR=1.0; 95%CI:0.6-1.8; P=0.95), homozygous BRM-1321 (OR=0.59; 95%CI:0.3-1.0; P=0.07) or double homozygous variants in both loci (OR=0.69; 95%CI:0.3-1.4; P=0.29). No association between BRM-741/BRM-1321 and OS and TTP was detected (For homozygous BRM-741, OS P=0.74, TTP P=0.93; for homozygous BRM-1321 OS P=0.39, TTP P=0.93). Consistently, there was also no association between double homozygous variants and OS and TTP (Double homozygous, OS P=0.64, TTP P=0.48). Heterozygous variants were also not associated with either risk or outcome.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Results of this study do not support use of BRM promoter polymorphisms as susceptibility or prognostic markers for thymoma. Molecular biologic mechanisms of risk and prognosis remain elusive in malignant thymoma.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA11.07 - Discussant - OA 11.04, OA 11.05, OA 11.06 (ID 14567)

      14:35 - 14:50  |  Presenting Author(s): Giuseppe Giaccone

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    WS03 - Endoscopic Diagnosis and Staging of Lung Cancer – Interventional Pulmonology Hands-On Workshop (Ticketed Session) (ID 986)

    • Event: WCLC 2018
    • Type: Workshop
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 4
    • Moderators:
    • Coordinates: 9/23/2018, 08:00 - 11:30, Room 205 BD
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      WS03.02 - EBUS-TBNA – Role in Invasive Mediastinal Staging (ID 14658)

      08:10 - 08:30  |  Presenting Author(s): Kazuhiro Yasufuku

      • Abstract
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      • Slides

      Abstract not provided

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      WS03.03 - Combined EBUS/EUS Mediastinal Staging (ID 14659)

      08:30 - 08:50  |  Presenting Author(s): Waël C. Hanna

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      WS03.04 - Radial Probe EBUS – Methods and Results (ID 14660)

      08:50 - 09:10  |  Presenting Author(s): Kasia Czarnecka-Kujawa

      • Abstract
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      Abstract not provided

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      WS03.05 - Navigational Bronchoscopy (ID 14661)

      09:10 - 09:30  |  Presenting Author(s): Laura Donahoe

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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